Protective and restorative role of Myristica fragrans essential oil on testicular and endocrine dysfunction induced by bisphenol A
Background: Bisphenol A (BPA) is a widely used endocrine-disrupting chemical that impairs male reproductive health through oxidative stress, hormonal imbalance, and testicular damage. Myristica fragrans (MF), rich in bioactive monoterpenes and phenylpropanoids, has demonstrated antioxidant and hormone-modulating properties, suggesting potential for reproductive protection. Aim: To evaluate the protective and restorative effects of M. fragrans essential oil against BPA-induced reproductive and endocrine toxicity in male rats and to correlate these effects with the oil’s chemical composition as identified by gas chromatography–mass spectrometry (GC–MS) analysis. Methods: Forty adult male rats were divided into four groups (n = 10): control (distilled water), MF-only (200 mg/ kg/day), BPA-only (50 mg/kg/day), and BPA + MF (co-treatment). All substances were orally administered for 60 consecutive days. Assessments included sperm motility, viability, morphology, and concentration; chromatin and deoxyribonucleic acid (DNA) integrity (via toluidine blue, aniline blue, and acridine orange stains); serum testosterone and luteinizing hormone (LH) levels; testis weight; and oxidative stress biomarkers total antioxidant capacity (TAC) and malondialdehyde (MDA). The essential oil composition was analyzed via GC–MS. Results: BPA exposure significantly impaired sperm quality, disrupted chromatin condensation and DNA integrity, altered hormone levels (↓testosterone, ↑LH), reduced testicular weight, and elevated oxidative stress markers (↑MDA, ↓TAC) (p < 0.001). Co-treatment with MF significantly restored all evaluated parameters to near-normal levels (p < 0.001 vs. BPA). GC–MS analysis identified sabinene (33.55%), α-pinene (23.08%), β-pinene (14.88%), and myristicin (0.84%) as the major constituents. The MF-only group did not significantly differ from controls in the measured endpoints; however, this finding should not be interpreted as evidence of comprehensive safety. Conclusion: MFE improved the measured sperm quality parameters, endocrine profile, oxidative stress biomarkers, and staining-based cytochemical indicators of sperm nuclear quality in rats exposed to high-dose BPA. However, mating performance, pregnancy rate, litter size, and other direct fertility outcomes were not evaluated; therefore, these findings should not be interpreted as evidence of improved fertility. The observed improvements in sperm quality, chromatin integrity, hormonal profile, and oxidative stress markers suggest that the antioxidant properties of the oil may be associated with its protective effects. However, the precise molecular mechanisms underlying these effects require further investigation.